The present invention relates to the field of medicine. More particularly, the invention relates to means for reversibly blocking the electric activity of cells. In particular, the invention relates to a method and means for reversibly blocking the muscle activity of various muscles (also referred to hereinafter as xe2x80x9cfencingxe2x80x9d), including the cardiac muscle.
Many activities of the human body involve the contraction of muscles. For instance, movement of the limbs, breathing activity, etc. The most complex and vital muscular activity of the human body is that of the heart, which functions as a pump and which, by contracting at the required times and in the required manner, controls the flow of blood throughout the body.
The heart is composed of different parts, which contract differently and with different timing, in order to permit the aforementioned pumping activity. The contraction of the heart is controlled by electric stimuli, which are generated at the cellular level by chemical reaction. However, it is well known in the art to control such activity, i.e., the timing of the contraction of the cardiac muscle, by the action of externally applied electric stimuli, through the so-called xe2x80x9cpace makerxe2x80x9d.
In a copending PCT patent application No. PCT/IL97/00012, filed Jan. 8, 1997, the specification of which is incorporated herein by reference, of which the inventors herein are also inventors, there is described a method and apparatus for modifying the force contraction of at least a portion of a heart chamber, which comprises applying a non-excitatory electric field, for a predetermined period of time, at a delay after activation.
In the aforesaid PCT patent application No. PCT/IL97/00012 and in another copending PCT/IL patent application of the same applicants herein, filed on the same day as the present application, entitled xe2x80x9cApparatus and Method for Controlling the Contractility of Musclesxe2x80x9d, and identified as Ser. No. 09/254,994, the specification of which is incorporated herein by reference, there is described a method and apparatus for decreasing the force contraction of at least a portion of a heart chamber, which comprises applying a non-excitatory electric field, for a predetermined period of time, at a delay after activation. The ability to reduce the contractility is of importance in a variety of situations, e.g., during surgery or as an aid in healing of hibernated areas of a heart after myocardial infarct.
The mechanical activity of excitable cells is directly connected to their electric activity. This is most evident in the activity of the heart, which has a relatively complex electric functioning which is responsible for pacing, contraction of various areas of the cardiac muscle, as well as to the organized consecutive or simultaneous contraction of various zones. Any disturbance in the electric function of the cells may severely affect, or even stop mechanical activities of the cell. Conduction problems are also related to a variety of congenital and acquired diseases. A detailed discussion of such phenomena can be found, e.g., in the book by Donald M. Bers, xe2x80x9cExcitation-Contraction Coupling and Cardiac Contractile Forcexe2x80x9d, Kluwer Academic Publishers, Dordrecut, Boston, London, 1993.
Treatment of electrical cellular malfunctioning is mainly confined to systemic treatment, such as by drugs or, in some cases with heart diseases, a pace maker may be required. Localized treatment, such as local ablation, is also sometime attempted. However, there are several conditions that cannot be treated by localized treatment, unless the activity of the relevant muscle is totally blocked for a suitable period of time, in a reversible manner. One example of such a condition is ventricular fibrillation or ventricular tachycardia arrhythmias, which can be induced by abnormal activity localized in a susceptible area.
Another important tool in heart therapy is the use of defibrillators. Defibrillation is a process in which an electronic device helps reestablish normal contraction rhythms in a heart that is not functioning properly, by delivering an electric shock to the heart. Defibrillators can be external or internal (implanted or inserted). Typically, a defibrillator is designed to automatically detect episodes of bradycardia, ventricular tachycardia (VT), fast ventricular tachycardia (FVT), and ventricular fibrillation (VF). When an arrhythmia is detected, the device will deliver the programmed pacing, cardioversion or defibrillation therapy. The device typically has two electrodes which are implanted. The defibrillator, as said, stops arrhythmia by delivering an electric shock, which is a painful and harmful treatment, particularly if repeated often and, importantly, it is not a localized treatment, but rather it is applied to the whole cardiac muscle.
It has now been surprisingly found, and this is an object of the present invention, that it is possible to block the activity of a localized area of cells, such as a muscle (i.e., to carry out axe2x80x9cfencingxe2x80x9d), in a reversible manner, and thus to block the cell""s activity for a desired period of time.
It is an object of the invention to provide apparatus for carrying out the fencing of a desired tissue area having electric activity and thereby temporarily and reversibly blocking the activity of said area.
It is another object of the invention to provide a method for treating a patient suffering from a condition treatable by temporarily blocking the electric activity of a tissue.
It is yet another object of the invention to provide a method and apparatus useful in therapy, which can be exploited in treating a variety of conditions, such as epilepsy, arrhythmia, stooping ticks, and shockless defibrillation.
Other objects and advantages of the invention will become apparent as the description proceeds.
In one aspect, the invention relates to apparatus for blocking the electric activity of an area of a tissue comprising circuitry for creating a long non-excitatory electric potential (LNT) between at least two points located in the vicinity of a muscle.
According to a preferred embodiment of the invention, the apparatus comprises circuitry for controlling the start time of the electric potential generated between said at least two points. According to another preferred embodiment of the invention, the apparatus comprises circuitry for controlling the duration of the electric potential generated between said at least two points. According to still another preferred embodiment of the invention, the apparatus comprises circuitry for controlling the magnitude of the electric potential generated between said at least two points.
The apparatus of the invention is particularly useful when the tissue on which it is employed is a cardiac muscle.
According to a preferred embodiment of the invention, the circuitry for creating a long non-excitatory electric potential between said at least two points comprises one or more electrode, e.g., carbon electrodes.
According to another preferred embodiment of the invention, the apparatus comprises circuitry for causing a long non-excitatory electric current to flow between at least two points located in the vicinity of a muscle.
The apparatus of the invention is useful, inter alia, for performing heart surgery, and comprises circuitry for creating a long non-excitatory electric potential between at least two points located in the vicinity of the cardiac muscle. According to another preferred embodiment of the invention, the apparatus comprises circuitry for causing a long non-excitatory electric current to flow between at least two points located in the vicinity of the cardiac muscle.
Illustrative examples of heart surgery in which the device of the invention can be utilized are a bypass operation and other minimal invasive cardiac operation.
The invention is further directed to a method for blocking the mechanical and/or electric activity of an area of a tissue, comprising creating a long non-excitatory electric potential between at least two points located in the vicinity of the tissue, and controlling one or more of the parameters consisting of start time, duration, magnitude and polarity of the long non-excitatory electric potential created between said at least two points. According to a preferred embodiment of the invention, the method for blocking the electric activity of an area of a tissue comprises causing a long non-excitatory electric current to flow between at least two points located in the vicinity of the tissue, and controlling one or more of the parameters consisting of start time, duration, magnitude and polarity of the long non-excitatory electric current flowing between said at least two points.
The invention also encompasses a method for performing heart surgery, comprising blocking the mechanical and/or electric activity of a treated area of the cardiac muscle, by creating a long non-excitatory electric signal between at least two points located in the vicinity of the muscle, and controlling one or more of the parameters consisting of start time, duration, magnitude and polarity of said long non-excitatory electric signal, thereby to obtain the desired blocking of the mechanical and/or electric activity of the cardiac muscle at the treated heart area and thereafter performing surgery thereon.
In one aspect, the invention is directed to a method for blocking the mechanical and/or electric activity of an area of a tissue, comprising:
providing means for creating an electric potential between at least two points located in the vicinity of said area of the tissue;
providing means for causing a non-excitatory electric current to flow between said at least two point; and
controlling the start time, duration and magnitude of the electric current flowing between said at least two points, such that the total duration of the long non-excitatory electric signal exceeds the threshold value at which the activity of the tissue is blocked.
In another aspect the invention is directed to a method of treating a condition induced by electric activity of cells, comprising treating a patient in need thereof with the application of a long non-excitatory signal between at least two points located in the vicinity of the affected cells, such that the total duration of the long non-excitatory electric signal exceeds the threshold value at which the electric activity of the tissue is blocked.
According to a preferred embodiment of the invention, the apparatus comprises the means for controlling the start time, duration and magnitude of the electric current flowing between said at least two points located in the vicinity of an area of the tissue comprise pulse generating means for generating a plurality of pulses, with a given frequency, and wherein the timing of said pulses is adapted to the activity of the tissue, the total duration of said series of pulses constituting the duration of the long non-excitatory signal.
The invention is also directed to defibrillating apparatus comprising circuitry for creating a long non-excitatory electric potential between at least two points located in the vicinity of a muscle, and to a method for carrying out a defibrillation in a patient in need thereof, comprising blocking the electric activity of an area of a tissue, comprising creating a long non-excitatory electric potential between at least two points located in the vicinity of the tissue, and controlling one or more of the parameters consisting of start time, duration, magnitude and polarity of the long non-excitatory electric potential created between said at least two points until defibrillation is achieved. According to a preferred embodiment of the invention, the method comprises causing a long non-excitatory electric current to flow between at least two points located in the vicinity of the tissue, and controlling one or more of the parameters consisting of start time, duration, magnitude and polarity of the long non-excitatory electric current flowing between said at least two points until defibrillation is achieved.
As will be apparent to the skilled person, the LNT-signal must be timed so as to have a delay relative to the activity of the muscle. If this is not taken into account a deleterious effect may result. For instance, when the cardiac muscle is treated, fibrillation may be induced by an electric signal which is not properly timed. Additionally, the LNT-signal will typically be composed of a plurality of short peaks, applied at a given frequency, and the total length of time during which said short peaks are applied constitutes the total duration of the LNT-signal. In order to deal with the above needs, in a preferred embodiment of the invention the means for controlling the start time, duration and magnitude of the electric current flowing between said at least two points located in the vicinity of an area of the tissue, comprise pulse generating means for generating a plurality of pulses, with a given frequency, and wherein the timing of said pulses is adapted to the activity of the tissue, the total duration of said series of pulses constituting the duration of the long non-excitatory signal.
According to a preferred embodiment of the invention there is provided a defibrillating apparatus for the localized and selective defibrillation at one or more locations of a heart, comprising for each of said one or more locations:
a) sensing means for sensing a change in electric activity of the heart or of a portion thereof;
b) analyzing circuitry, for analyzing said change in electric activity;
c) logic circuitry, for deciding on the appropriate therapy to be delivered to the sensed area or to the area of the heart which is responsible for the change in electric activity, said appropriate therapy comprising the application to the affected area of a long non-excitatory signal of a suitable magnitude, start time, duration and frequency;
d) signal delivery means, for delivering said long non-excitatory signal to said area of the heart; and
e) control means, for controlling the delivery of said long non-excitatory signals to each affected area, and for timing the delivery of different signals to two or more different affected areas of the heart.
The signal delivery means can be of various suitable types and may include, e.g., one or more electrodes.
In the context of the present invention, by xe2x80x9clong non-excitatory currentxe2x80x9d, or xe2x80x9clong non-excitatory potentialxe2x80x9d, or xe2x80x9clong non-excitatory signalxe2x80x9d, it is meant to indicate a signal which does not cause a propagating action potential in the muscle cells (which may start a new pacing or contraction of the muscle). In other words, the non-excitatory electric stimulation effected by a non-excitatory electric pulse is such that it does not induce propagating activation potentials in the cardiac muscle cells. Rather, such pulses affect the response of the heart muscle to the action potentials, by affecting cell electrical characteristics within selected segments of the cardiac muscle.
As described in the abovementioned PCT patent application PCT/IL97/00012, while a DC current is typically used as the base line for the non-excitatory signal, it is also possible to supply a signal which is a complex signal, for instance, a signal generated by superimposing an AC current on the DC base signal, so as to generate a waveform of varying envelope. Any suitable signal can be superimposed, having any shape, e.g., square wave or sinusoidal wave, as will be apparent to the skilled person. Thus, according to one preferred embodiment of the invention the apparatus further comprises means for superimposing on a DC signal one or more waveforms of given frequency and amplitude, thereby to generate a complex signal.
The apparatus can be provided in various forms, depending on the specific needs. One example of apparatus suitable for carrying out the invention is described in detail and claimed in a copending PCT patent application of the same applicants herein, entitled xe2x80x9cCardiac Output Controllerxe2x80x9d, filed on the same day as the present application and identified as Ser. No. 09/254,902, the description of which is incorporated herein by reference. Another example of suitable apparatus, coupled to a pacemaker device, is the subject of another copending PCT patent application of the same applicants herein, entitled xe2x80x9cCardiac Output Enhanced Pacemakerxe2x80x9d, filed on the same day as the present application and identified as Ser. No. 09/254,900, the specification of which is also incorporated herein by reference. However, as said, the invention is not intended to be limited to any particular construction of device used to carry it out.
According to a preferred embodiment of the invention, the apparatus is intended for long term treatment, and is an insertable device. An insertable device is a device which can be introduced for a limited period of time (i.e., up to a few weeks), for a prolonged therapy. It differs from an implanted device inasmuch as it is not meant to be carried by the patient indefinitely or for very long periods of time. According to another preferred embodiment the apparatus can be implantable. According to still another preferred embodiment of the invention, the apparatus, whether intended for short or long term treatment, is an extra corporal device.
As explained above, the means for causing a non-excitatory DC electric current to flow, are preferably synchronized to heart activity. According to a preferred embodiment of the invention, the means for causing a non-excitatory DC electric current to flow operate not at every beat of the heart, e.g., operate every 1, 2 or 3 beats of the heart.
As will be appreciated by the skilled person, the actual set of operating parameters used (current, length of pulse, number of electrodes, lag after pacing signal, etc.), will be dependent on the specific use made of the invention, and the skilled person will easily be able to devise the optimal set of parameters for a given application. Where no pace maker is used, the delay is preferably calculated from the natural activity of the patient""s heart, or from the local electrical activity.
The invention can be conveniently carried out using sensing means coupled to control means, which sense the electric activity of the muscle and activate the LNT-signal at the appropriate time.
It should further be noted that, while in the above discussion and in the examples to follow particular emphasis has been put on cardiac muscles, this has been done only for the purpose of illustration, and the invention is by no means meant to be limited in any way to cardiac muscle. On the contrary, the invention is applicable to other tissue which has an activity which is dependent on electric signals.
While a variety of electrodes can be used, and the invention is in no way limited to any particular type of electrode, particularly preferred suitable electrodes for this purpose are, e.g., carbon electrodes.